1. Field of the Invention
The present invention relates generally to the field of prosthetic and orthopedic devices. More particularly, it concerns prosthetic devices having porous tissue-mating surfaces impregnated with a biodegradable material, such as a biodegradable polymer. The invention also relates to methods of preparing and using such devices.
2. Description of the Related Art
Every year many people require artificial hip, knee or shoulder implants (prostheses). Although such total joint prostheses have been in clinical use for decades, they are still plagued with problems associated with inadequate permanent, rigid fixation. Virtually all implants currently in use have a tendency to loosen with time, some to the extent of requiring revision.
There are two main techniques commonly used for fixation: cemented types using bone cement and uncemented or press-fit types. In cemented devices, a bone cement in common use is poly(-methyl methacrylate). This cement is applied in a dough-like state as a grouting agent between the bone and the implant. It flows around the contours of the bone and the implant and into the interstices of cancellous bone. Upon hardening, the cement forms a mechanical interlock between the bone and the implant. In effect, there is no bone in-growth linking bone and prosthesis when bone cement is used. Although bone cement gives good initial fixation, an increase in compliance often occurs due to formation of a soft tissue capsule over time. Thus, the absence of bone in-growth frequently leads to loosening of a bonecemented prosthesis.
Press-fit prostheses are not implanted with bone cement but rather into a prepared cavity in the bone which closely approximates the prosthetic shape; long term stability of such implants requires bone to form an interlock by growing into the prosthesis at the mating surface. Both porous and mesh type mating surfaces have been employed on press-fit prostheses to enhance fixation in bone, with various materials coated on the surfaces to allow desired bone growth.
Certain osteoconductive materials (e.g., hydroxyl-apatite applied by plasma-spraying) are favored for their durability and bonding strength, but obtaining the desired press-fit at surgery is often associated with problems (Geesink, R. G. T., Clinical Orthopedics and Related Research, 261:39-58 (1990)). Further, the cavity prepared in bone to receive the prosthesis is generally not optimally shaped, causing the actual bone contact achieved with insertion of the prosthesis to be only 10-20% of the potential mating surface. The remaining voids between bone and prosthesis, containing little or no osteoconductive material, decrease and/or impair the bone-prosthesis interlock necessary for long-term stability of the prosthesis.
Conventional press-fit prosthesis often provide inferior long-term fixation to bone because of inadequate and/or inconsistent bony in-growth. A porous surface on a prosthesis facilitates some minimal enhancement of bony in-growth. Thus, the overall use of a prosthesis with such a porous surface provides inferior long-term rigid fixation. A need remains in the medical arts for a press-fit device that achieves sufficient rigid fixation so as to be suitable for long-term prosthetic use.
The feasibility of achieving fixation of prostheses using bone in-growth is well established. However, studies have shown that clinically the bone in-growth is both inconsistent and inadequate (Collier et al. (1988), Clinical Orthopaedics and Related Research, 235:173-180). In a study of 226 retrieved porous-coated implants, Collier et al. determined that only 25% of femoral and 16 percent of acetabular components exhibited any significant bone in-growth. In an attempt to increase the degree of in-growth, some studies have successfully used rat marrow cells in HA implants in a rodent model (Ohgushi et al. (1992) J. Biomed. Mater., 26:885-895). Recently Miller et al. have described the use of an osteogenic protein in HA implants (Miller et al. (1991) Plas. Reconstr. Surg., 87:87-95). Implants with this protein showed a significant increase in the amount of bone in-growth compared to the controls of HA implants without the protein in a rabbit model. However, no mechanical testing of the interface was performed.
A protein with osteogenic properties was first identified in demineralized bone by Urist (Urist, M. R. (1965), Science, 150:893-895). This substance was termed bone morphogenetic protein (BMP) (Urist and Strates (1971), J. Dental Res., 50:1392-1406). BMP derived from human, bovine, and porcine sources has been shown to exhibit osteogenic activity in rats indicating that it is not species specific (Aldinger et al. (1991), International Orthop. (SICOT), 15:169-177). Because of the difficulty in isolating large amounts of purified BMP from bone, recombinant human proteins (BMP 2-5) have been expressed from a cDNA library prepared from the U20S human osteosarcoma and other cell lines. Of these recombinant proteins, BMP2, 4, and 5 have been shown to maintain their osteogenic potential after purification (D'Alesandro et al. (1991), J. Cell. Biochem. 515F, p. 166).
The presence of exogenous osteogenic protein has been reported to enhance bone in-growth into a hydroxyapatite implant in a rat model (Miller et al. (1991) Plas. Reconstr. Surg., 87:87-95). U.S. Pat. No. 4,563,489 describes the combination of BMP and biodegradable polylacatic acid polymer that is implanted in viable tissue where the BMP is slowly released. However, the potential of using exogenous BMP at a bone surface to enhance bone in-growth or strengthen the bone-prosthesis interface at the surface of a bone prosthetic device has not been explored to any significant degree in the literature.
Another known protein that is osteogenic in nature is TGF.beta. (Joyce, M E, (1990), J. Cell Biol., 110:2197-2207; Noda, M. (1989), Endocrinology, 124:2991-2994). The use of this particular protein in enhancing fracture healing as a result of local application of exogenous TGF.beta. in adult animals is discussed in Lind et al. (1993, 39th Meeting, Orthopaedic Research Society, February, 1993, San Francisco, Calif.). Use of TGF.beta., as well as other growth factors as a clinical tool in bone healing has also been proposed (Id.). Schakenraad et al. (Biomaterials, 9:116-20 (1988)), describe the development of a biodegradable hollow fiber of poly (l-lactide) for controlled release of contraceptive hormone.
A problem that exits in available drug or agent-treated prosthetic devices is that they typically release the drug or agent in relatively short, not therapeutically useful periods of time. This is due to at least two factors, (1) the immediate release of drug at an implant surface and (2) the relatively longer period of release necessary to provide therapeutic advantage. Thus, such devices are not particularly well suited for long term prosthetic implants.
The above review illustrates the need in the medical arts for prosthetic devices that enhance rigid fixation at prosthesis-tissue mating surfaces, and allow improved boney in-growth. Improved methods for controlling release of active agents at the surface of a press-fit prosthetic device over therapeutically useful periods of time are also needed.